Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B

Anna S.F. Lok, Ching Lung Lai, Nancy Leung, Guang Bi Yao, Zhen Yu Cui, Eugene R. Schiff, Jules L. Dienstag, E. Jenny Heathcote, Nancy R. Little, Dorothea A. Griffiths, Stephen D. Gardner, Mary Castiglia

Research output: Contribution to journalArticlepeer-review

688 Scopus citations


Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of the lamivudine-treated patients in year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine resistance resistant stable during the first 4 years with mutations and increased afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.

Original languageEnglish (US)
Pages (from-to)1714-1722
Number of pages9
Issue number6
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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